CN101974107A - 一种酯化物的分离方法 - Google Patents

一种酯化物的分离方法 Download PDF

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CN101974107A
CN101974107A CN 201010287144 CN201010287144A CN101974107A CN 101974107 A CN101974107 A CN 101974107A CN 201010287144 CN201010287144 CN 201010287144 CN 201010287144 A CN201010287144 A CN 201010287144A CN 101974107 A CN101974107 A CN 101974107A
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precipitate
ethanol
throw out
precipitation
purified water
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CN101974107B (zh
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刘伟
李加耀
王秀萍
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DONGYING TIANDONG PHARMACEUTICAL CO LTD
Shandong Haike Chemical Co ltd
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SHANDONG HI-TECH CHEMICAL GROUP Co Ltd
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Abstract

本发明涉及一种依诺肝素的生化制品的一种中间品的制备方法,特别涉及一种酯化物的分离方法。其技术方案是:依诺肝素生产至酯化完成后,加入乙醇(含1~5%乙酸钠)用量为酯化液的1.5~3倍量,沉淀放置2~24h后,去上清,搅拌下加入沉淀溶液总体积2%~20%的纯化水,再补加入纯化水1.5~3倍量体积的乙醇,加水至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物,沉淀物加入氯化钠溶解成5%~20%浓度,加入乙醇,至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物。克服了传统工艺生产气味较大,有毒气体挥发对人体和环境有危害且不宜大规模生产等缺陷,且稳定性好,产品收率正常。

Description

一种酯化物的分离方法
一、技术领域:
本发明涉及一种依诺肝素的生化制品的一种中间品的制备方法,特别涉及一种酯化物的分离方法。
二、背景技术:
依诺肝素钠是肝素钠经β-消除法降解制备,具有抗凝血酶III(ATIII)依赖性抗Xa因子活性,对体内、外血栓,动、静脉血栓的形成有抑制作用。酯化物作为依诺肝素钠生产过程中的一种中间品,常规工艺制备气味较大,有毒气体挥发对人体和环境有危害且不宜大规模生产。
三、发明内容:
本发明的目的就是针对现有技术存在的上述缺陷,提供一种酯化物的分离方法,克服了传统工艺生产气味较大,有毒气体挥发对人体和环境有危害且不宜大规模生产等缺陷,且稳定性好,产品收率正常。
其技术方案是:依诺肝素生产至酯化完成后,加入90%~95%浓度乙醇,含1~5%乙酸钠(w/v重量体积比),用量为酯化液的1.5~3倍量,沉淀放置2~24h后,去上清,搅拌下加入沉淀溶液总体积2%~20%的纯化水,再补加入纯化水1.5~3倍量体积的乙醇,加水至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物,沉淀物加入1%~5%的氯化钠溶解成5%~20%浓度,加入1.5~3倍量90%~95%浓度乙醇,至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物。
本发明的与传统分离方法相比具有以下优势:
1.反应可以在密闭容器中进行,避免了离心时气味较大,有毒气体挥发对人体的危害;
2.由于不在暴露空气中操作,避免了环境污染的可能性;
3.可以加大生产规模,避免小作坊式操作;
4.操作简便,易于掌握,人员技术要求不高;
5.缩短了生产周期。
四、附图说明:
附图1是本发明的流程示意图。
五、具体实施方式:
结合附图,对本发明作进一步的描述,以下采用w/v重量体积比:
依诺肝素生产至酯化完成后,加入90%~95%浓度乙醇(含1~5%乙酸钠,w/v重量体积比),用量为酯化液的1.5~3倍量,沉淀放置2~24h后,去上清,搅拌下加入沉淀溶液总体积2%~20%的纯化水,再补加入纯化水1.5~3倍量体积的乙醇,加水至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物,沉淀物加入1%~5%的氯化钠溶解成5%~20%浓度,加入1.5~3倍量90%~95%浓度乙醇,至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物。
乙醇用量增加,相应费用也有加大,不过废乙醇可以通过蒸馏回收后继续使用,实际损耗约为5%,在可以接受的范围内。

Claims (1)

1.一种酯化物的分离方法,其特征是:依诺肝素生产至酯化完成后,加入90%~95%浓度乙醇,含1~5%乙酸钠,为w/v重量体积比,用量为酯化液的1.5~3倍量,沉淀放置2~24h后,去上清,搅拌下加入沉淀溶液总体积2%~20%的纯化水,再补加入纯化水1.5~3倍量体积的乙醇,加水至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物,沉淀物加入1%~5%的氯化钠溶解成5%~20%浓度,加入1.5~3倍量90%~95%浓度乙醇,至沉淀物形成,沉淀放置2~12h后,去上清得沉淀物。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109293800A (zh) * 2018-08-16 2019-02-01 山东万邦赛诺康生化制药股份有限公司 一种肝素卞酯生产过程中氯化苄味道去除办法
WO2019116217A2 (en) 2017-12-11 2019-06-20 Biological E Limited Process for the preparation of low molecular weight heparin

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09143199A (ja) * 1995-11-17 1997-06-03 Nippon Chem Res Kk 血小板第4因子の製造方法
CN101165071A (zh) * 2006-10-20 2008-04-23 江苏江山制药有限公司 依诺肝素及其制备方法
CN101463095A (zh) * 2007-12-20 2009-06-24 大英县茂森生物化工厂 肝素生产新工艺
CN101824099A (zh) * 2010-02-12 2010-09-08 淮安麦德森化学有限公司 一种粗品肝素钠的纯化方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09143199A (ja) * 1995-11-17 1997-06-03 Nippon Chem Res Kk 血小板第4因子の製造方法
CN101165071A (zh) * 2006-10-20 2008-04-23 江苏江山制药有限公司 依诺肝素及其制备方法
CN101463095A (zh) * 2007-12-20 2009-06-24 大英县茂森生物化工厂 肝素生产新工艺
CN101824099A (zh) * 2010-02-12 2010-09-08 淮安麦德森化学有限公司 一种粗品肝素钠的纯化方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019116217A2 (en) 2017-12-11 2019-06-20 Biological E Limited Process for the preparation of low molecular weight heparin
US11299558B2 (en) 2017-12-11 2022-04-12 Biological E Limited Process for the preparation of low molecular weight heparin
CN109293800A (zh) * 2018-08-16 2019-02-01 山东万邦赛诺康生化制药股份有限公司 一种肝素卞酯生产过程中氯化苄味道去除办法

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